tbuckley/cabot-search huggingface dataset:
A scalable approach to democratizing cancer risk stratification: One healthcare system’s approach using a patient-facing digital platform.
Authors: Heather Fecteau, Dax Kurbegov, Reena Manhar Patel, Haley Keller, Carolyn Horton, Lily Hoang, Shannon M. Kieran
Journal: Journal of Clinical Oncology (2023)

10622 Background: Access to genetic testing and risk stratification is primarily gated by referrals from non-genetics providers for patients who meet testing criteria. The majority of Americans seek care at community hospitals that are closer to home; community hospitals are faced with the challenge of how to democratize access to precision oncology and cancer prevention. Research has shown that the establishment of such protocols is challenging, requiring organizational buy-in, capital, resources, and the involvement of multiple levels of clinical and nonclinical stakeholders. Here we highlight Sarah Cannon, the Cancer Institute of HCA Healthcare, and their programmatic approach to risk stratification using a digital platform offered universally to all patients undergoing screening mammography. Methods: From February to November in 2022, fourteen sites were assessed to have appropriate provider and facility capabilities to support the implement the CARE program. The web-based risk-stratification tool is sent to individuals before standard ambulatory appointments to assess their lifetime risk for breast cancer based on the Tyrer-Cuzick (version 8.0) risk algorithm and National Comprehensive Cancer Network (NCCN) genetic testing criteria. Testing criteria included hereditary breast, ovarian, pancreatic, and prostate cancers, Lynch syndrome, and familial adenomatous polyposis (FAP). Retrospective data was pulled from patients seen between February 2022 through January 2023. The outcome measures included percentage of individuals who completed the risk-assessment, met genetic testing criteria, pursued germline genetic testing, received a positive germline result, and/or had a breast cancer risk ≥20%. Results: During the 10 months at the 14 community hospitals a total of 25,671 individuals were invited for risk assessment through the CARE program; 19,277 (75.1%) individuals completed assessment. Overall, 5,070 (26.3%) met genetic testing criteria and 1,536 individuals had a ≥20% lifetime risk of breast cancer, for a total of 34% of patients identified as elevated risk. 23.4% (1,187) of those meeting criteria opted to proceed with germline genetic testing. An additional 126 individuals who did not meet criteria pursued genetic testing. Of the 1,313 completed genetic tests, 96 (7%) had positive genetic test results. Fifty-four of 96 (56%) positive results had an impact on medical management and cancer prevention. Conclusions: Sarah Cannon and HCA Healthcare have successfully begun implementing a comprehensive, digital risk stratification program in the community hospital setting to provide standardized access to genomic testing and risk stratification. By identifying patients with an elevated risk for cancer, the potential for increased early cancer detection and precision oncology can be observed in a scalable and sustainable program.
Evaluation of potential socioeconomic and racial/ethnic disparities in all-cause mortality in adolescent and young adult patients with cancer.
Authors: Scott Henderson, Mark Duggan, Chun Chao, Robert Michael Cooper
Journal: Journal of Clinical Oncology (2023)

6501 Background: Adolescent Young Adult (AYA) cancer patients, aged 15-39, have historically been understudied. For older adults, socioeconomic (SES) and racial/ethnic disparities in mortality have been demonstrated, but less is known about survival disparities for AYA patients. Most existing studies do not account for the influence of insurance status and access to care. To address this gap, we evaluated the association of SES and race/ethnicity with overall mortality for AYA cancer patients who were members of an integrated health delivery system with relatively equal access to care. Methods: Patients diagnosed with cancer at age 15-39 years old in Kaiser Permanente Southern California between 2010-2018 were included. The fourteen most common AYA cancer types within our cohort were included (excluding thyroid cancer due to low mortality rate). The Neighborhood Deprivation Index (NDI) was used as a marker of SES. Patients were placed into NDI quartiles (Q1: least deprived-Q4: most deprived). Mortality rate per 1,000 patient years was calculated for each racial/ethnic group and NDI quartile. Multivariable cox model was used to estimate hazard ratios (HRs) for all-cause mortality. Models included race/ethnicity and NDI subgroup simultaneously, adjusting for sex, age and stage at diagnosis, and cancer type. Results: A total of 6,380 patients (59% female, median age: 33) were followed for a maximum of ten years. Racial/ethnic distribution was 45% Hispanic, 36% non-Hispanic White, 10% non-Hispanic Asian/Pacific Islander, 7% non-Hispanic Black, 2% Other/Unknown. Overall mortality was 21.8 deaths per 1,000 person years. Crude mortality rates were higher among Non-White racial/ethnic groups (Asian/Pacific Islander: 26.7, Black: 26.2, Hispanic: 25.6, Other/Unknown: 30.3) compared to White patients (16.4). In the adjusted model, Hispanic (HR=1.32, 95% confidence interval [CI] 1.03-1.50, p=0.004) and Black (HR=1.35, 95% CI 1.00-1.83, p=0.05) patients experienced significantly higher risk of all-cause mortality compared to White patients. No mortality differences were observed between Asian/Pacific Islander and White patients. Patients from more deprived neighborhoods had higher mortality risk (Q1: 19.9, Q2: 19.8, Q3: 24.1, Q4: 27.4). In the adjusted model, there was no significant difference in all-cause mortality between Q1 and Q2-Q4 [Q2 (HR=0.88, 95% CI 0.71-1.10), Q3 (HR=0.94, 95% CI 0.75-1.17), Q4 (HR=0.96, 95% CI 0.76-1.22)]. Conclusions: Our study suggests that for insured AYA cancer patients with similar access to care, Hispanic and Black patients have increased risk of all-cause mortality as compared to White patients, while no significant SES survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.
Phase Ib/IIa study assessing the safety and efficacy of AL8326 monotherapy in patients with ≥3rd line small cell lung cancer (SCLC) treatment.
Authors: Xiaochun Zhang, Xingya Li, Minghong Bi, Chunxia Su, Yong Fang, Zibing WANG, Ying Yuan, Xiuping Du, Tangfeng Lv, Yingyin Li
Journal: Journal of Clinical Oncology (2023)

8585 Background: AL8326 is a novel, orally administered, small molecule tyrosine kinase inhibitor (TKI). The primary objective of this Phase Ib/IIa study is to evaluate the safety and efficacy of AL8326 monotherapy in patients with ≥3rd line small cell lung cancer (SCLC) treatment. Methods: Patients with a diagnosis of small cell lung cancer either limited or extended stage requiring third or further line treatment were eligible for enrollment. The regimen was a 28-day cycle with oral AL8326 administered at 60 mg once per day via RECISIT1.1 evaluation until disease progression (PD), or intolerable toxicity or any other reason discontinuations. Results: At the cut-off date Nov 30, 2022, total n = 30 patients were enrolled. The objective response rate (ORR) was 20% (6/30) (4 confirmed). The disease control rate (DCR) was 56.7% (17/30). Median progression-free survival (PFS) was 3.65 months (95% CI: 1.9 – 5.5) and median overall survival (OS) was 10.42 months (95% CI: 5.4, NE). The median duration of response (DOR) was 5.6months. All 30 subjects had reported AE at least once. Common treatment emergent adverse events (TEAE) were similar to other TKI drug and included (incidence ≥20%): thyroid stimulating hormone (TSH) increase (46.67%), proteinuria (43.33%), weight loss (40.00%), hypertension (36.67%), thrombocytopenia (33.33%), diarrhea (33.33%), positive fecal occult blood (30.00%), hypercholesterolemia (26.67%), hypertriglyceridemia (26.67%), hand- foot syndrome (HFS) (20.00%), loss of appetite (20.00%). Most of these AEs were grade 1-2 (CTCAE V5.0). Conclusions: AL8326 has demonstrated acceptable tolerability and positive efficacy on small cell lung cancer treatment. A US Phase 2 (NCT05363280) study is ongoing and a phase 3 study is in preparation. Clinical trial information: NCT04890795 .
Analysis of demographic characteristics of malignant peripheral nerve sheath tumor in adults: A National Cancer Database study.
Authors: Caitlyn Voth, Xinxin Wu, Darby Keirns, Peter T. Silberstein, Beau Hsia
Journal: Journal of Clinical Oncology (2023)

e23555 Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare cancer involving the peripheral nerve sheath. Even though the 5-year post-surgical resection survival rate is only 30 to 40%, the epidemiology is not well understood, and looking at trends in demographics could provide insight into factors potentially contributing to poor prognosis. A previous National Cancer Database (NCDB) study investigated demographics in pediatric patients with MPNST. This study analyzed NCDB data to investigate the demographics of adults with MPNST. Methods: Adult patients with a histologic diagnosis of MPNST were retrospectively examined in a cohort analysis using demographic information from the NCDB from 2004 – 2020 (N = 414). Regression analysis was used to describe incidence trends. Demographics (age, sex, race, Hispanic origin, income, insurance status, area of residence, facility type, distance from facility, and Charlson-Deyo score) were explored through descriptive statistics. Palliative care enrollment and mortality rate was examined. Results: 414 patients with age &gt; 18 were identified in the NCDB database with a confirmed diagnosis of MPNST between the years 2004 – 2020. There was a slight increase in incidence of patients diagnosed per year (R2 = 0.254). The average age of diagnosis was 47.0 years (SD = 17.2, range = 19 – 88 years) with more males (51.4%) affected than females (48.6%). The most common primary sites were the retroperitoneum (32.4%), spinal cord (24.4%), and cranial nerves (15.0%). A majority of individuals (82.6%) had Charlson-Deyo comorbidity scores of 0. Individuals most commonly affected were White (79.7%) or Black (14.3%), and non-Hispanic (87.4%). Patients most commonly were in the top quartile of household income (31.6%), had private insurance (53.6%), lived in metropolitan counties (83.8%), and received treatment at an academic/research program (62.2%). Patients lived on average 61.6 miles (SD = 145.7, range = 0.5 – 1454.9) from the facility. The 90-day mortality rate post-surgery was 10.5%. The overwhelming majority of patients did not receive palliative care (94.4%). Conclusions: This is the first NCDB analysis on the demographics of MPNST in adults, providing information that bridges the gap in knowledge. This analysis showed that the retroperitoneum was the most common tumor site, and that the average age of diagnosis was 47 years, consistent with previous reports. Patients were most likely to be White, non-Hispanic, upper quartile income earners, privately insured, treated at an academic facility, and live in metropolitan counties. With the majority of patients receiving no palliative care, it’s possible that palliative care is underutilized and may benefit MPNST patients given the poor prognosis. Additional research on the relationship between socioeconomic status and palliative care access may provide information on this discrepancy.
Evaluating differences in cancer survivorship care plans experienced by cancer survivors with disabilities.
Authors: Hermine Poghosyan, Sayantani Sarkar
Journal: Journal of Clinical Oncology (2023)

e18597 Background: Survivorship Care Plans (SCPs) are crucial elements for short- and long-term follow-up care among cancer survivors and have been endorsed by leading oncologic organizations. Yet, limited research exists about the receipt of SCPs among survivors with disabilities who may face additional barriers to access the health care services. Our study examines the association between the disability status and receipt of SCPs after completion of cancer treatment among US adult cancer survivors. Methods: This secondary analysis included cross-sectional, nationally representative, population-based data from the 2021 Behavioral Risk Factor Surveillance System. We included 2110 respondents (aged ≥ 18 years) who self-reported cancer history (other than skin cancer). Outcomes were self-reported receipt of cancer treatment summaries and follow-up care instructions after completion of the cancer treatment. The independent variable was disability status, comprised of six specific disability types (having serious difficulty with hearing, vision, cognition, mobility, self-care, and independent living). We combined disability status into four groups—as having 1) no disability; 2) one disability; 3) two disabilities; and 4) three or more disabilities. We applied recommended sample weights and conducted weighted descriptive statistics and multivariable logistic regression adjusting for self-reported individual-level factors (age, sex, race, marital status, education, health insurance, provider type who provided majority of the care). Results: Overall, 4.2% self-reported as Black, 19.5% Hispanic, 70.0% White, 59.5% women, and 54.5% aged 65+ years. A total of 20.8% of participants reported having one disability, 11.1% two disabilities, and 11.7% reported three or more disabilities. Mobility disability was the most prevalent disability type (27.0%), followed by cognition (14.8%), independent living (14.5%), hearing (12.7%), vision (9.2%), and self-care (6.5%). About 18.0% did not receive follow-up care instructions, and 41.7% did not receive treatment summaries. Overall, 52.8% of survivors reported receiving both follow-up care instructions and treatment summaries. Survivors with three or more disabilities were 0.40 (95% CI 0.27-0.88, p = 0.019) times significantly less likely to report receiving follow-up care instructions than survivors without disabilities. Survivors’ disability status was not significantly associated with reporting the receipt of cancer treatment summaries. Conclusions: Nearly half of the survivors did not receive SCP upon treatment completion, which may lead to poor treatment adherence and deterioration of health. Our findings suggest disparities in follow-up instructions based on disability status, especially for people with multiple disabilities. Effective strategies are necessary to build more equitable cancer survivorship care.
A phase II study of fruquintinib in the first- (1L) or second-line (2L) treatment of unresectable metastatic soft tissue sarcoma.
Authors: Zhiguo Luo, Xiaowei Zhang, Ting Zhao, Bi-Qiang Zheng, Wangjun Yan, Yong Chen, Yu Xu, Chun-Meng Wang, Junhua Zhang, Jian Wang, Lin Yu, Xin Liu
Journal: Journal of Clinical Oncology (2023)

e23547 Background: Standard treatment for patients with unresectable metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if fruquintinib, a highly selective tyrosine kinase inhibitor of VEGFR-1, -2, and -3 is effective and safe in the 1L or 2L treatment for these patients. Methods: This is a single-arm, prospective, single-center clinical study. The inclusion criteria were patients with pathologically confirmed unresectable metastatic STS (including desmoplastic small round cell tumors, epithelioid hemangioendothelioma, hemangiopericytoma/malignant solitary fibroma, and chemotherapy-failed hemangiosarcoma), at least one measurable lesion (according to RECIST 1.1), with the normal function of main organs. Other inclusion criteria included ECOG PS 0-2 and anti-angiogenesis treatment naïve. Patients were administrated 5mg fruquintinib once daily for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. The primary study endpoint was Progression free survival (PFS). Objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and adverse event was also calculated. Results: Data cutoff date was January 31 2023. 14 patients (9 males and 5 females) were enrolled. The median age is 50.1 (range 21-69). Pathological types included: Hemangiopericytoma/malignant solitary fibroma (n=6); Epithelioid Hemangioendothelioma (n=6) and Hemangiosarcoma (n=2). 2 patients were died, the median PFS was 8.1 m. 14 patients were eligible for the evaluation of tumor response. 3 patients (2 cases of Hemangiosarcoma and 1 case of Epithelioid Hemangioendothelioma) achieved partial response (PR) and the ORR was 21.4 %(3/14). 10 patients had stable disease (SD) and the DCR was 92.9% (13/14). Most adverse events were hypertension, fatigue, and hemorrhage. The most Grade 3/4 adverse effect is hypertension and abnormal liver function. Conclusions: The fruquintinib showed a promising efficacy and favorable tolerance in the 1L or 2L treatment of unresectable metastatic soft-tissue sarcoma. Clinical trial information: NCT05142631 .
Comprehensive genomic and transcriptomic profiling analysis of the recurrent gastrointestinal stromal tumor (GIST).
Authors: Lu Sun, Xiaohui Wang, Xin Wu, Fengwei Zhu, Liu Hong, Wen Chen, Yingshi Piao, Hong Luo, Yiqun Zhang, Ling Liu, Yuehua Zang, Wenjing Li, Zhihua Pei, Dongliang Wang, Qiming Zhou, Huaiyin Shi
Journal: Journal of Clinical Oncology (2023)

e23506 Background: The gastrointestinal stromal tumor (GIST) is a potentially malignant mesenchymal tumor (sarcoma), whose management has been transformed by approvals of TKIs. However, recurrence or metastasis is a formidable challenge in managing high-risk GIST. Comprehensive investigation of the transcriptome and genome in GIST is helpful to determine the therapy strategy for patients. This study aims to explore the molecular features of high-risk recurrence GIST. Methods: The tumor tissue samples of 42 patients with primary GIST were collected, in which all patients were divided into low-risk (n = 12), intermediate-risk (n = 11), and high-risk (n = 19) groups according to the NIH 2017 th , in which 8 developed recurrence within three years and 11 without recurrence over three years in the high-risk group. Tumor-normal whole-exome and tumor mRNA sequencing was performed on baseline tissue DNA isolated from all patients. Results: Consistent with prior knowledge, KIT was the predominant mutation. The top mutated genes in GISTs were KIT (82%), PHLDA1 (39%), MUC6 (22%), ARID1B(20%), SURF2(20%), MGA(16%), MUC17(16%), MPRIP(16%) and PDGFRA(16%), which MUC6 was a significantly different mutation gene (DMG) associated with disease progression in terms of either high-risk(p = 0.04), recurrence(p = 0.02) or progression(p = 0.05). Interestingly, PDGFRA mutation co-occurs with CTNND2(p &lt; 0.01) and its correlated genes. Additionally, we further explored the somatic copy number variations (CNVs). amp_RAD51B(49%), amp_MLH3(41%), amp_CHEK2(37%), and amp_RB1(12%) seemed to be more frequent in the recurrence group, while these observations were not significant (p &gt; 0.05). Notably, del_NCOR1 or amp_NCOR1 was uniquely observed in the recurrence group. Compared with non-recurrence GIST, gene expression profiles revealed that mast cell activate (MCA)，M1-macrophages infiltration were higher in recurrence group, and mRNA was significantly upregulated in Systemic lupus erythematosus、Neutrophil extracellular trap formation、Viral carcinogenesis、Endocytosis. These pathways were indentified as being associated with recurrence and progression in other cancer studies. For example, the endocytosis pathway expression is positively associated with oncogenic pathway signaling in CRC, and neutrophil extracellular trap on cancer cells promotes liver metastasis in the tumor microenvironment. In the other, NCOR1 is a crucial regulator of T cell and B cell development. Conclusions: Here, we demonstrated the DNA/RNA profiles of GISTs. We observed higher CNVs in high-risk GIST. Especially, the high-risk recurred tumor presented different CNVs frequency and microenvironment. These results may contribute to understanding the mechanism of recurrence and improving recurrence detection.
Twenty-year patterns in area deprivation index and risk of metastatic prostate cancer at initial diagnosis among men in Ohio.
Authors: Jennifer Cullen, Julia Yang Payne, Stephen Paul Rhodes, Jonathan Evan Shoag
Journal: Journal of Clinical Oncology (2023)

10526 Background: Men diagnosed with prostate cancer (PCa) have a 5-year overall survival (OS) rate of 98%. However, this rate plummets to approximately 30% for men diagnosed with metastatic PCa. Furthermore, PCa exerts a greater burden on African American men with a higher incidence and a higher mortality rate than other races. These disparities have been contributed to a result of interactions among genes, health behaviors, and access to care. In our study, we examined Social Determinants of Health (SDoH) – social risk factors that contribute to disparities in cancer mortality. Area deprivation index (ADI) is one of the assessments used to measure these social risk factors. ADI can assess a geographic area’s level of socioeconomic deprivation and is associated with health outcomes on the census block level. Variables used in ADI are grouped into 4 domains – education, income, employment, and housing quality. Most of the communities will fall between a standardized score of 40 to 160. In this study, we used a large population-based cancer database to examine the impact of ADI on risk of metastatic PCa at diagnosis in Ohio. Methods: The Ohio Cancer Incidence Surveillance System (OCISS) data were examined for the period 1996 to 2016 to predict the odds of distant stage at diagnosis. Generalized additive models were constructed with age and year of cancer diagnosis, area deprivation index, race, and Hispanic ethnicity as predictors. The relationship between continuous variables and odds of distant diagnosis was modeled via penalized cubic splines. Odds ratios were calculated for race and Hispanic ethnicity. To summarize the results for variables modeled via splines, predicted probabilities were calculated with other variables held at their average or reference values. Results: We identified 112,023 men with PCa in OCISS database. The median age was 67 (IQR 61-67) years old. Subjects were 85.3% White, 13.8% Black, and 0.9% other races. Only 0.6% of men were Hispanic. By stage, 84.6% (N=94753) had localized PCa, 10.4% (N=11640) had regional PCa, and 5.0% (N=5571) had distant PCa. The median ADI was 93.9 (IQR 83.6-106.5). Our analysis showed that Black men had 41.8% higher odds of having metastatic PCa at diagnosis than White men. Furthermore, our analysis showed similar risk of metastatic PCa at diagnosis in lower ADI values but higher risk at higher ADI values (Table). Conclusions: Higher ADI values were associated with higher risk of metastatic PCa at diagnosis. Interventions should target populations with socioeconomic deprivation and aim to improve patient access to prostate cancer prevention, screening, and treatment services. [Table: see text]